Transcriptome Sequencing Identified Hub Pathogenic Chemokines In Atherosclerotic Plaques

Atherosclerotic plaque (AP) is a kind of inflammatory fibrous tissue proliferative disease after the injury of endothelial cells and smooth muscle cells in the artery wall, which can lead to different degrees of cardiovascular and cerebrovascular blood flow obstruction. However, effective therapeutic approaches targeting inflammation have largely failed to date, suggesting that additional insights remain needed. In this study aimed to analyze inflammatory factor-related transcriptomic changes in AP using RNA-sequencing (RNA-seq). RNA-seq was performed on samples from AP patients (n = 11) and control individuals (n = 3). Differentially expressed genes (DEGs) were identified using Metascape, followed by KEGG pathway enrichment analysis using clusterProfiler package in R software, immune infiltration analysis using CIBERSORT, and protein-protein interaction (PPI) network using STRING database. Hub genes within the PPI network were identified using the CytoHubba plugin. A total of 3713 DEGs were identified in AP group, including 2097 up-regulated and 1616 down-regulated genes. The results showed that DEGs were mainly enriched in immune- and inflammation-related pathways. Three inflammation-related factors CCL3, CCL4, and CXCL1 were considered as major hub genes in the pathological process of AP. Immune infiltration analysis revealed a distinct microenvironment in AP, characterized by a significant increase in M0 macrophages alongside reductions in CD8⁺ T cells, activated NK cells, and resting mast cells within AP. In conclusion, these procedural findings describe the differenrial expression of CCL3, CCL4, and CXCL1 and their association with an altered immune cell composition in AP, highlighting the three chemokines as potential candidates for further mechanistic investigation.